Purpose This study used Data Envelopment Analysis (DEA) to measure and evaluate the operational efficiency of 26 isolation hospitals in Egypt during the COVID-19 pandemic, as well as identifying the most important inputs affecting their efficiency. Design/methodology/approach To measure the operational efficiency of isolation hospitals, this paper combined three interrelated methodologies including DEA, sensitivity analysis and Tobit regression, as well as three inputs (number of physicians, number of nurses and number of beds) and three outputs (number of infections, number of recoveries and number of deaths). Available data were analyzed through R v.4.0.1 software to achieve the study purpose. Findings Based on DEA analysis, out of 26 isolation hospitals, only 4 were found efficient according to CCR model and 12 out of 26 hospitals achieved efficiency under the BCC model, Tobit regression results confirmed that the number of nurses and the number of beds are common factors impacted the operational efficiency of isolation hospitals, while the number of physicians had no significant effect on efficiency. Research limitations/implications The limits of this study related to measuring the operational efficiency of isolation hospitals in Egypt considering the available data for the period from February to August 2020. DEA analysis can also be an important benchmarking tool for measuring the operational efficiency of isolation hospitals, for identifying their ability to utilize and allocate their resources in an optimal manner (Demand vs Capacity Dilemma), which in turn, encountering this pandemic and protect citizens' health. Originality/value Despite the intensity of studies that dealt with measuring hospital efficiency, this study to the best of our knowledge is one of the first attempts to measure the efficiency of hospitals in Egypt in times of health' crisis, especially, during the COVID-19 pandemic, to identify the best allocation of resources to achieve the highest level of efficiency during this pandemic.